Treatment of thalassaemia: a review of the new approaches on transfusion safety and the novel therapeutics

Lifetime red cell concentrate (RCC) transfusions still account for significant iron overload‐related morbidity and mortality despite chelation therapy in thalassaemia. The cumulative risk of transfusion‐transmitted infections is substantial for thalassaemia patients. Pathogen reduction technologies for RCC may imply a proactive approach against new/re‐emerging pathogens and may be an ultimate safeguard for transfusion safety in the developing countries. Red cell alloimmunization may become a significant clinical challenge in thalassaemia. The availability of high‐throughput molecular blood group antigen typing in the donors may allow perfect match transfusion, beyond ABO‐D and CEK antigen‐matched transfusions. Allogeneic stem cell transplantation (A‐SCT) is the only available curative therapy in thalassaemia, but carries a substantial risk of serious adverse events and mortality. Gene addition therapy for correction of the α‐globin chain imbalance overcomes the problems of donor availability and immunological complications of A‐SCT. Gene editing by either gene disruption or correction emerged as a potential alternative to gene addition therapy in beta‐thalassaemia. A new era of novel therapeutics targeting α/β imbalance, ineffective erythropoiesis or iron dysregulation is unfolding in thalassaemia management, and a number of those now have agents in preclinical and clinical development. Hydroxyurea (HU) may improve globin chain imbalance and be beneficial for reducing or omitting transfusion requirement. Ruxolitinib has allowed steady decrease in spleen volume that may serve for avoiding splenectomy in beta‐thalassaemia. Luspatercept may restore normal erythroid differentiation and improve anaemia. Hepcidin mimetics or TMPRSS6 inhibitors may modulate ineffective erythropoiesis by iron restriction and improve anaemia and organ iron loading.     

放射性碘对大鼠致癌效应的研究

对雄性Wisiaf大鼠腹腔1次注射碘-13l, 注入活度分别为0.59×10⁴Bq,2.37×10⁴Bq, 4.34×10⁴Bq, 8.23×10⁴Bq, 碘-125注入活度分别为3.7×10⁴Bq, 7.4×10⁴Bq, 14.8×10⁴Bq, 22.2×10⁴Bq.碘-131诱发肿痛实际注入活度在2.37×10⁴Bq以下,碘-125的为7.4×10⁴以下.诱发的肿瘤以甲状腺肿瘤为主,其次为垂体肿瘤.     

经肝动脉灌注^131 I-HAblSF（ab’）2治疗肝癌合并门静脉癌栓疗效分析

目的探讨经肝动脉灌注^131 I-HAbl8F（ab’）2治疗肝癌合并门脉癌栓的价值。方法8例合并门脉癌栓的晚期肝癌患者行经肝动脉超选择灌注^131 I-HAbl8F（ab＇）2临床治疗性试验，剂量：0．75mCi／kg。分析症状、卡氏评分、肝功能、AFP及肿瘤CT等影像变化，随访近期疗效。结果7例疼痛患者中，3例症状缓解。3例卡氏评分增加、4例稳定。6例AFP异常患者治疗后3例下降。全组病例用药后肝功能损害均无明显加重。1例无明显症状的弥漫型肝癌患者治疗后病灶减少；余7例中，瘤体增大5例、缩小2例，其中，PR2例，临床有效率28．6％。本组1例1年随访时生存。结论经肝动脉灌注0．75mCi／kg ^131 I-HAbl8F（ab＇）2对合并门脉癌栓的肝癌患者肝功影响小，对门脉分支癌栓患者有较好的疗效。     

National intercomparisons of I radioactivity measurements in nuclear medicine centres in India

National intercomparisons of activity measurements of ¹³¹I, a radioisotope widely used for diagnosis and therapy of thyroid related ailments, were initiated in 1979 as a quality assurance program, towards improving radiation safety procedures and related dosimetry in Nuclear Medicine Centres (NMCs) in India. Oral administration of a known quantity of radioiodine to patients requires accurate radioactivity measurements to be performed on a well-calibrated isotope calibrators. Under or over estimation of the activity due to a faulty or uncalibrated isotope calibrator could provide misleading results. Calibration of isotope calibrators and the traceablity of subsequent measurements to the national standards laboratory is one of the essential basic radiation safety requirement of the IAEA. In view of the stringent quality assurance requirements for activity measurements imposed by Atomic Energy Regulatory Board, a National Intercomparison Program was initiated and to date ten such intercomparison programs have been conducted by the Radiation Safety Systems Division, of the Bhabha Atomic Research Centre. This program has benefited the participants by making their measurements traceable to the National Primary Standards. Over the years there has been a marked increase in the number of NMCs participating in the intercomparison programs. As a result, the number of institution showing large deviation from the correct value has decreased considerably over the years. This program thus, has enabled participating NMCs to check their isotope calibrators so as to ensure proper delivery of radiation dose to the patients and hence to optimise patient exposure.     

放射性碘在大鼠甲状腺内的滞留模式及剂量估算

为确定放射性碘在甲状腺内滞留模式，观察甲状腺吸收放射性碘后的生物效应，进而评价其辐射危害。方法利用活体测量方法，直接测量两个不同年龄组大鼠甲状腺内１３１Ⅰ的代谢参数。对测量数据进行处理后得到了大鼠甲状腺内１３１Ⅰ的滞留函数为三指数项函数。结果利用所得三指数项滞留函数的准确方法进行剂量估算，所得的两组动物的甲状腺平均累积吸收剂量分别为７．７Ｇｙ和１１．５Ｇｙ，而一般方法算得的大鼠甲状腺的平均累积吸收剂量比用准确方法高估了６６％～９１％。结论由于准确方法考虑到影响估算甲状腺所受剂量的一些因素，故可相对准确地反映了１３１Ⅰ所致不同年龄大鼠甲状腺的吸收剂量。     

131I对甲状腺细胞凋亡的影响

由于每个患者特异性基因决定的个体辐射敏感性不同,使得每个接受131I治疗的患者对治疗的反应不一,因而疗效差异较大.针对不同的个体,采用不同的剂量治疗才可以提高131I治疗的效率,降低甲状腺功能减退症的发病率.通过目前的分子生物学技术,我们已经了解到一些基因的蛋白表达产物(Fas/FasL、Bcl-2等)与细胞凋亡和射线诱导凋亡的联系,使对凋亡基因表达产物的体外监测成为可能.也许通过对这些指标的监测,可以使我们在131I治疗过程中实现对不同的个体给予恰当的个体剂量.     

血清Tg、TgAb对甲状腺癌根治术联合131I治疗后随访期间复发/转移的评估价值

目的 研究血清甲状腺球蛋白（Tg）、甲状腺球蛋白抗体（TgAb）对甲状腺癌根治术联合¹³¹I治疗后随访期间复发/转移的评估价值。方法 回顾性分析2018年6月—2020年6月中国贵航集团三〇二医院收治的106例分化型甲状腺癌患者的临床资料,患者均接受甲状腺癌根治术治疗,术后均采用¹³¹I进行清除残留的甲状腺组织（清甲）治疗。随访24个月,将患者分为复发转移组（21例）和未复发转移组（85例）。比较两组临床资料、¹³¹I治疗情况及血清促甲状腺激素（TSH）、Tg、TgAb。绘制受试者工作特征（ROC）曲线分析血清Tg、TgAb检测对甲状腺癌根治术联合¹³¹I治疗后复发/转移的预测价值。采取非条件一般Logistic回归模型进行多因素分析。结果 与未复发转移组比较,复发转移组原位肿瘤T₄分期、手术方式为腺叶切除或近全切、残余甲状腺质量≥1 g、手术至¹³¹I治疗时间> 3个月、24 h摄¹³¹I率≤ 20%患者的占比均较高（P <0.05）;复发转移组血清Tg和TgAb水平均较高（P <0.05）;ROC曲线分析结果显示：血清Tg预测甲状腺癌根治术联合¹³¹I治疗后复发或转移的最佳截断值为1.674 μg/L,AUC为0.803（95% CI：0.721,0.884）,敏感性为81.1%（95% CI：0.724,0.898）,特异性为63.8%（95% CI：0.585,0.691）;血清TgAb预测的最佳截断值为44.19 3 IU/mL,AUC为0.911（95% CI：0.859,0.963）,敏感性为89.2%（95% CI：0.813,0.971）,特异性为72.5%（95% CI：0.674,0.774）。非条件Logistic一般回归分析结果显示：原位肿瘤T₄分期［O^R=2.916（95% CI：1.325,6.417）］、腺叶切除或近全切［O^R=3.243（95% CI：2.174,4.838）］、残余甲状腺质量≥ 10 g［O^R=1.835（95% CI：1.514,2.224）］、手术至¹³¹I治疗时间> 3个月［O^R=1.962（95% CI：1.371,2.808）］、24 h摄¹³¹I率≤ 20%［O^R=2.638（95% CI：1.219,5.709）］、血清Tg ≥ 1.674 μg/L［O^R=2.503（95% CI：1.430,4.360）］、血清TgAb≥ 44.193 IU/mL［O^R=2.944（95% CI：2.016,4.299）］可能是甲状腺癌根治术联合¹³¹I治疗后复发或转移的危险因素（P <0.05）;风险因素预测模型预测甲状腺癌根治术联合¹³¹I治疗后复发/转移的ROC曲线下面积为0.961（95% CI：0.935,0.987）,标准误为0.010,临界值为73.162,敏感性为91.9%（95% CI：0.863,0.957）,特异性为88.2%（95% CI：0.845,0.922）。结论 甲状腺癌根治术联合¹³¹I治疗后出现复发/转移的患者血清Tg、TgAb水平明显升高,Tg、TgAb对预测复发/转移具有较好的价值,联合其他危险因素建立风险因素预测模型可进一步提高预测价值。     

Graves‘甲亢^131I治疗前后TGA,TMA的变化及临床意义

本文对502例Graves'病患者的甲状腺功能及TGA、TMA水平进行了观察,按治疗前TGA、TMA水平分为两组,第一组为阳性组(TGA>30%,TMA>15%),第二组为阴性组。结果显示,阳性组早发甲低率明显高于阴性组(p<0.01),其临床治愈率也高于阴性组(p<0.01);而阴性组治疗后临床症状缓解不全者明显高于阳性组。提示Graves'甲亢~(131)Ⅰ治疗前后,测定TGA、TMA有一定的临床指导意义,对于治疗前设计剂量方案及预测甲低的发生均有一定的参考价值。     

放射性药品生产单位雾化固定高浓度131I放射性气溶胶的初步研究

目的 验证雾化固定技术用于控制高浓度¹³¹I气溶胶的可行性。方法 对国内某放射性药品生产单位操作¹³¹I的手套箱内高浓度¹³¹I气溶胶实施雾化固定。测量箱式内¹³¹I气溶胶浓度,进行结果分析。结果 手套箱内（289 ±9） DAC和（304 ±6） DAC的¹³¹I气溶胶,固定处理120 min后,气溶胶浓度分别降至（21.7 ±2.0） DAC和（26.2 ±1.8） DAC;手套箱内（259 ±10） DAC的¹³¹I气溶胶,固定处理180 min后,气溶胶降至（1.80 ±0.18） DAC;固定完成24 h后检测结果表明,没有发生气溶胶再悬浮。结论 雾化固定技术可以在较短时间内有效控制有限空间内¹³¹I气溶胶浓度,降低工作人员内照射风险,可用于放射性药品生产单位作为处理高浓度¹³¹I气溶胶的应急管理办法。